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dc.contributor.authorTalbot, Jessica J
dc.contributor.authorSubedi, Shradha
dc.contributor.authorHalliday, Catriona L
dc.contributor.authorHibbs, David E
dc.contributor.authorLai, Felcia
dc.contributor.authorLopez-Ruiz, Francisco J
dc.contributor.authorHarper, Lincoln
dc.contributor.authorPark, Robert F
dc.contributor.authorCuddy, William S
dc.contributor.authorBiswas, Chayanika
dc.contributor.authorCooley, Louise
dc.contributor.authorCarter, Dee
dc.contributor.authorSorrell, Tania C
dc.contributor.authorBarrs, Vanessa R
dc.contributor.authorChen, Sharon C-A
dc.description.abstractBackground: The prevalence of azole resistance in Aspergillus fumigatus is uncertain in Australia. Azole exposure may select for resistance. We investigated the frequency of azole resistance in a large number of clinical and environmental isolates. Methods: A. fumigatus isolates [148 human, 21 animal and 185 environmental strains from air (n = 6) and azole-exposed (n = 64) or azole-naive (n = 115) environments] were screened for azole resistance using the VIPcheck™ system. MICs were determined using the Sensititre™ YeastOne YO10 assay. Sequencing of the Aspergillus cyp51A gene and promoter region was performed for azole-resistant isolates, and cyp51A homology protein modelling undertaken. Results: Non-WT MICs/MICs at the epidemiological cut-off value of one or more azoles were observed for 3/148 (2%) human isolates but not amongst animal, or environmental, isolates. All three isolates grew on at least one azole-supplemented well based on VIPcheck™ screening. For isolates 9 and 32, the itraconazole and posaconazole MICs were 1 mg/L (voriconazole MICs 0.12 mg/L); isolate 129 had itraconazole, posaconazole and voriconazole MICs of >16, 1 and 8 mg/L, respectively. Soil isolates from azole-exposed and azole-naive environments had similar geometric mean MICs of itraconazole, posaconazole and voriconazole (P > 0.05). A G54R mutation was identified in the isolates exhibiting itraconazole and posaconazole resistance, and the TR34/L98H mutation in the pan-azole-resistant isolate. cyp51A modelling predicted that the G54R mutation would prevent binding of itraconazole and posaconazole to the haem complex. Conclusions: Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates; further surveillance is indicated.
dc.publisherOxford University Press
dc.relation.ispartofjournalJournal of Antimicrobial Chemotherapy
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsInfectious Diseases
dc.subject.keywordsPharmacology & Pharmacy
dc.titleSurveillance for azole resistance in clinical and environmental isolates of Aspergillus fumigatus in Australia and cyp51A homology modelling of azole-resistant isolates
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationTalbot, JJ; Subedi, S; Halliday, CL; Hibbs, DE; Lai, F; Lopez-Ruiz, FJ; Harper, L; Park, RF; Cuddy, WS; Biswas, C; Cooley, L; Carter, D; Sorrell, TC; Barrs, VR; Chen, SC-A, Surveillance for azole resistance in clinical and environmental isolates of Aspergillus fumigatus in Australia and cyp51A homology modelling of azole-resistant isolates,Journal of Antimicrobial Chemotherapy, 2018, 73 (9), pp. 2347-2351
gro.hasfulltextNo Full Text
gro.griffith.authorSubedi, Shradha

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